Confirmation that T cell receptor activation is digital, not analog. Hence individual T cell cytolytic capacity is independent of initial stimulation strength

TL;DR

This study confirms that T cell activation responses are digital, meaning individual T cells respond in an all-or-none manner regardless of the initial stimulus strength, which has implications for understanding immune responses.

Contribution

The paper provides experimental evidence that T cell activation is digital across different stimuli, extending previous findings to pMHC-activated T cells.

Findings

T cell responses are digital regardless of stimulus strength

Early transcriptional and metabolic changes are similar across stimuli

Individual T cell cytolytic capacity is independent of initial stimulation

Abstract

Whether a sub-optimum lymphocyte stimulus is achieved by lowering ligand concentration, or decreasing its affinity, initial TCR activation responses are likely to be digital. We now know for cultured peripheral blood mononuclear cells (PBMCs), when activated by plant lectins such as concanavalin-A (Con-A), that the responding cells are T cells, and that early transcriptional and metabolic changes closely resemble those found with T cells responding to specific peptides complexed to MHC proteins (pMHC). Robbins long ago showed that lectin-activated PBMC responses were digital. This has now been confirmed for pMHC-activated T cells. Hence, in general, responses of individual T cells are independent of initial signal strength.